Orgenesis' ORG-101, a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy, has shown promising efficacy and safety results in a real-world study involving 233 patients with CD19+ B-cell acute lymphoblastic leukemia (ALL) treated at a leading hematology center in China. The data suggest that ORG-101 could offer a valuable treatment option for both adult and pediatric ALL patients.
Efficacy and Safety Data
The study revealed a complete response (CR) rate of 82% in adult patients and 93% in pediatric patients treated with ORG-101. These results indicate a strong therapeutic effect in a challenging patient population. In terms of safety, the incidence of severe cytokine release syndrome (CRS) was notably low, with only 2% of treated adults and 6% of treated children experiencing this complication. Orgenesis emphasizes that these severe CRS rates are lower compared to those observed with currently approved CAR-T therapies.
Decentralized Manufacturing Approach
ORG-101 is manufactured using a third-generation lentiviral vector coding for a proprietary CAR construct. What sets ORG-101 apart is its decentralized manufacturing approach, where production and analytic testing are conducted onsite. This contrasts with the centralized manufacturing model typically used for traditional CAR-T therapies. Orgenesis believes that this decentralized approach has the potential to improve access to CAR-T therapy and reduce costs, addressing key challenges in the widespread adoption of these treatments.
Regulatory Pathway and Future Trials
Orgenesis has engaged in discussions with regulatory bodies, including the FDA, the Ministry of Health of Israel, and Germany's Paul-Ehrlich-Institute, regarding the development of ORG-101. The company plans to advance ORG-101 into a multicenter phase 1/2 clinical trial, with the General University Hospital of Patras in Greece slated to be the first site for the trial, supported by an Enterprise Greece Grant.
Industry Context
The positive data on ORG-101 coincides with recent approvals of other CAR-T therapies in China. Legend Biotech's ciltacabtagene autoleucel (cilta-cel), marketed as Carvykti in the United States and Europe, received approval from China’s National Medical Products Administration (NMPA) for the treatment of adults with relapsed or refractory (r/r) multiple myeloma (MM) who have previously received at least three lines of therapy. Additionally, JW Therapeutics’ relmacabtagene autoleucel injection (relma-cel), marketed as Carteyva, was approved for the treatment of adults with r/r mantle cell lymphoma (MCL) who have received at least two prior lines of systemic therapy, including a bruton tyrosine kinase inhibitor. These approvals underscore the growing importance of CAR-T therapies in treating hematologic malignancies in China.
Management Commentary
"We believe that these clinical results combined with our Good Manufacturing Practice-Validated Platform are a significant step forward for our strategy to combine our strong capabilities in decentralized cell therapy production with our regional partnerships," said Vered Caplan, CEO of Orgenesis. "Not only has the product shown initial signs of positive clinical outcomes, but our production data also validated that Orgenesis’ cost-effective decentralized cell processing has the potential to improve access to this treatment and reduce costs. We remain committed to bringing this and other potentially life-saving treatments to patients in need worldwide."
